Method of making substituted guanidines



Dec. 9, 1930.

R. v. HEusER 1,784,442

METHOD OF MAKING SUBSTITUTED GUANIDINES Filed March 5, 1925 i, .u dOTOL/J/Q//vf T *l :Jr/59M Q 6 Q /Z /a/ jr/L y Q) J lJ'u///VE PAB P/P/Ef?24 @f PH M #iL/551i IN VEN TOR.

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l SN) `Patented Dec. 9, 1930 UNHE STATES PATENT oFFIcE RALPH VHEUSER, GFELIZABETH, NEW JERSEY, ASSIGNOR TO MERGAN CYANAMD CMEANY, GF NEW' YGRK,N. Y., A COR-EOR-ATION QF IvIAINE v METEODOF IVI-KENG SUESTITTEDGUANIDINES application ined March 5, 1925.` serial N. 13,208-

This invention relates to substituted guanidines, more particularly to amethod of making the same and to products thereof which are suitable foraccelerating the vul- V 5 canization of rubber.

This application is a continuationin part of my co-pending applicationSerial No. 1393, filed J an. 9th, 1925, for method of niakingdiphenylguanidine in Which l have described and claimed a method whichincludes producing cyanogen chloride free from substantial amountsof-chlorine and hydrochloric acid, and passing the same over aniline,whereby it is absorbed forming diphenylguanidine hydrochloride. Tohasten and complete the reactionv the aniline isheated. rlheproduct isthen purified and the free base is precipitated, Washedv and dried.

In continuing myexperiments,l discovered that the typeof reactionutilized by me in the production of diphenylguanidine may be used forthe production of other substituted guanidines. My experiments haveincluded researches on various homologues of benzol and Ihave foundthat, bythis general method l may make not only straight aryl guanidinesbut also mixed aryl guanidines as Well as guanidines having both aryland alkyl groups linked with nitrogen.-

For instance, I have prepared di-o-tolylguanidine by passingsubstantially pure cyanogen chloride into a steam acketed reactionkettle over the surface of heated o-toluidine, which absorbs the gasforming di-oo3 tolylguanidine hydrochloride and impuri- V' ties. Theresidual gas is scrubbed by fresh o-toluidine to remove therefrom anyunreaoted cyanogen chloride. rlhe mixture is subjected to steamdistillation to remove unreacted o-toluidine and the reaction product istreated first with a solution of soda ash and then with caustic sodasolution to first eliminate the basic impurities and then to precipitatethe pure di-otolylguanidine In the accompanying drawingA constituting apart hereof, the single figure is a diagrammatic view of a systemadapted for the practice of this invention. y

Cyanogen chloride, containing an excess of chlorine, is passed throughpipe 1 into the stirrer 5 is slowly revolved and steam is .z

passed into the jacket 6 to maintain a temperature in the vessel l ofabout 100 C. to complete the reaction and to keep the mass fluid. Thereacted mass is then transferred to still 9 through pipe 10 and steam isinjected through pipe 11, vaporizing the otoluidine, Which is liquefiedin condenser 12 and drops into the container 13. The o-toluidine maybeseparated from the Water and` with or Without further purification, beaddedto the o-toluidine in the vessel 4L by means of pipes 14 and 8. 1

rEhe di-o-tolylguanidine hydrochloride With basic impurities istransferred to tank 15 Where it is thoroughly mixed With a largequantity of Water 16. and a small amount of finely divided charcoal 17,such as Darcof and a suiiicient quantity of a Weak 2.5% sodium carbonatesolution 18 is added to render the solution slightly alkaline. Theamount of di-o-tolylguanidine hydrochloride in the solution should besmall, say not over 4%. 'The material is then filtered in 19 to removethe precipitated Weak bases, leaving practically nothing butdi-o-tolylguanidine hydrochloride, sodium chloride and some sodiumcarbonate Vin solution.

The filtered liquid is added slowly at first and then more rapidly tosufficiently v'dilute (approximately 6%) causticfsoda solution 20 inytank 21 to precipitate all of the di-o-tolylguanidine base, which ispractically insoluble at ordinary temperatures in very dilute causticsoda solutions containing sodium chloride` and also in Water, which isused for Washing the same. The material is filtered and washed in filter22 and is Lthen centrifuged and dried in the centrifugal 23 and drier24, respectively. A p A compounds, some of which are briefly describedbelow:

Di-mor p-tolylguanidine may be'made from mor p-toluidine and cyanogenchloride,

Di-o, 1nor p-amino-phenylguanidine may be .made from o, nr, orp-plienylenediamine andcyanogen chloride. Y

Di-m-V or p-am1notolylguanidines may be made fromy thc `propertoluencdiamiuc andy cyanogen chloride.

y "described andy vclaimed in the co-pending apex,

Phen'yl-oor p.-tolylguanidinei are Irepre Asentative of mixedsubstituted guanidines which may be ymade inaccordance with myinvention. ZI may vfirst lprepare and isolate phenyl cyanainid kby vtheinteraction of cyanogen chloride .and aniline, thereaction beingarrestedy at an intermediate stage, yas

'lication of John" L. Osborne and George arsky, which has matured intoPatent No.y 1,611,941, issued December' 28, 1926, for.

method of preparing'substituted cyalnamids. and.v assigned Vto theAmerican'r Cyanamid CoInpany.V The method consists in providing.alsolutionfof ari-aromatic amine'such'A as anilne, in water, passinggaseous' cyanogen ychloride vinto the solution to react lWiththe.yar'iiline, or the like, yto produce phenyl 'cyani- `amid,`pand keepingthe reaction mixture cool j E by meansof cooling water. The hydrochloricjacidV formed in the 'reaction is neutralizedas `it is formed by calciumcarbonate.` The phenyl. cyanamid, which may `'first be sub- 'jected to apuriicationtreatment, is'allowed to reactwith oor `toluidi`ne to formthe ,y spending mixe di-substituted guanidine.r f

Alkyly phenylguanidines, such as methyl phenylguanidine may beprepared-by the interactiono'f phenyl' cyanamid with methyl-y amine gasor the hydrochloride. Alkyl tolylguanidies ,mayy be madefin a similarmanuel' starting with tolyl cyanamid which is formed by the interactionof cyanogen chloride and toludine. Y

. Di-alkyl-phenyland tolylguanidines may be yprepared by reacting onphenylor tolyl cyanamid withy the corresponding di-alkyl aminehydrochloride,`rv such as di-metliylor di`ethyle`mine hydrochloride.

' Di-mcthyl disphenyl guan-idine` may be prepared by the interactionbetween one molecleofcyanogen chloride and two molecules of mono-methyla'nili'ne; Thertolylderivativesmay be similarly prepared.

AI anticipatefthat `all vof the above named compounds havepropertieswhich render de-r sira'ble the 'usf thereof -for the accelerationv of-thevul'canikz"ation of rubber. In particular those'compounds having analkyl group directly linked with nitrogen are 'very active.

For'instance/methyl phenylguanidine, hav'-Y Y. Y

maybe prepared by first providing a mixture .of ang-alkyl amine and anaryl amine and causing eyanogen chloridefto contact with the samein amanner similar to the vprocedure given above in detail yforthe'production ofV di-o-tolylguanidine. In making methylvphenylguanidine by this method I start vvvvitha mixture'of amethylamineandaniline.

From the above it will be seen that I may utilize tivo' methods .for thepreparation of substituted guanidines, the first of which maybeconsidered-a oneste method andthe other atwo step method. i' ey onestep'method is readily applicable although not limited to themanufacture Vof symmetrical idisubstitited guanidlnes'by the ldlrectreaction between cy,- anogen `chloride and a suitable amine.' The twostep'method is especially applicable"toY the Vmanufacture ofnon-symmetrical 'd-sub?.Y

Seemed guanidines although' if kmay be usedr to produce'ethe symmetricalcompounds as Well. This latter method consists'inrs't pro-l .vidingLv asuitablek substituted cyanarnid, such as phenyl or tolyl icyan'amid byany well known process and then causing the same to react with asuitable amine, such as methyl amine or aniline.

Although yI have describe'dmy invention 'setting forth a numbenofembodiments there`- of,'my invention vis not limited thereto,as manyother substances `ofsimilar character may be prepared inaccordance'yvithmy method. The method is simple, does not requirecomplicatedapparatus for the practice there- 'of,'close control thereofvis not necessary, and the kcflciencies are high, ymaking it extremelyeconomical. 1 These and other advantages are inherent in my invention,the scope of which is defined inthe claims appended hereto.

1. A methodof making substituted guanilines which comprises bringingcyanogen chloride, vvfreelfrom substantial amounts of chlorine andhyd'rocyanic acid, intocontact With a secondary' aryl-'alkyl amine andcans`` ius yno

Cil

placed by an alkyl group and causing a reaction to take placetherebetween in one operation. n

3. A method of making substituted guanidines which comprises bringingcyanogen chloride, tree from substantial amounts of chlorine andhydrocyanic acid, into contact with an aryl and an alkyl compound eachcontaining an NH2 group and causing a rey action to take 4placetherebetween.

e. A method of making substituted guanidines which comprises bringingcyanogeii' chloride, free from substantial amounts of chlorine andhydrocyanic acid, into contact with an alkyl compound containing an NH2group and causing a reaction to take place therebetween to 'formcli-substituted guanidines in one operation.

5. A method of making substituted guanidines which comprises bringingcyanogen chloride, iree 'rom substantial amounts ot chlorine andhydrocyanic acid, into contact with a hydrocarbon compound containing aplurality of NH2 groups, and causing a reaction to take placetherebetween.

6. A method of making substituted guanidines which comprises bringing'eyanogen chloride, free from substantial amounts of chlorine andhydrocyanic acid into Contact with an aryl amino compound containing areplaceable hydrogen in the amino'group and a methyl amine containing areplaceable hydrogen in the amino group, and causing a reaction to takeplace therebetween.

7. A method oi' making substituted guanidines which comprises bringingoyanogen chloride, free from substantial amounts of chlorine andhydrocyanie acid into contact with an aryl amino compound containing a.replaceable hydrogen in the amino group and mono-methyl amine, andcausing a reaction to take place therebetween.

S. A method of making substituted guanidines which comprises bringingcyanogen chloride, 'free from substantial amounts of chlorine andhydrocyanic acid, into Contact with aniline and a. methyl aminecontaining a replaceable hydrogen in the amino group, and causing areaction to take place therebetween.

9. A method ot making substituted guanidines which comprises bringingcyanogen chloride, free from substantial amounts of chlorine andhydrocyanic acid, into Contact with aniline and an alkyl aminecontaining a replaceable hydrogen in the amino group, and causing areaction to take place therebetween.

10. A method `of preparing substituted guanidines which comprisesbringing cyanogen chloride into contact with an aryl amine to form asubstituted cyanamid and causing said cyanamid to react with an alkylamine containing a replaceable hydrogen in the amino group.

In testimony whereof, I have hereunto subscribed my name this 27 th dayof February RALPH V. HEUSER.

